Hydro-responsive wound dressings for treating hard-to-heal wounds: a narrative review of the clinical evidence.

A break in skin integrity must be repaired as quickly as possible to avoid excess blood and fluid loss, and to minimise the onset of infection. Hard-to-heal wounds, in which the progression of the wound healing response is compromised, present several challenges to healing (for example, the presence of devitalised tissue acting as a physical barrier to healing and as a focus for bacterial contamination with the potential for subsequent infection). The objective of this article is to present, as a narrative review, the clinical evidence supporting the use of a unique hydro-responsive wound dressing (HydroClean, HRWD1, PAUL HARTMANN AG, Germany). The dressing provides a simple treatment option to address a number of clinical challenges clinicians must overcome in order to facilitate wound healing progression. These studies demonstrated that this product supported successful debridement/cleansing of a wide variety of wounds, including hard-to-heal wounds, enabled wound bed preparation, and lead to positive healing outcomes, including in wounds that previously had failed to heal. The simplicity of using HRWD1 as a single dressing can help clinicians overcome a variety of challenges when treating both acute and hard-to-heal wounds, which, with the benefit of proven patient outcomes, could make it an ideal choice for a first-line treatment.

Consultant-led triage of paediatric hospital referrals: a service evaluation.

Objective: We established a paediatric demand management (PDM) service in our paediatric department in 2017. The aim of this consultant-delivered service is to manage referrals more efficiently by providing active triage of all referrals, daily rapid access clinics and easily accessible advice for primary healthcare professionals. This study presents an evaluation of this service. Design: Mixed-methods service evaluation with analysis of data for every contact with the PDM service over a 2-year period. For each patient, the method of contact, reason for contact, presenting complaint and triage outcome were recorded. Feedback from general practitioners (GPs) and patients was gathered. Results: Data were analysed for 7162 patients. More than a quarter (2034; 28%) of all referrals were managed with advice only. Of the 4703 outpatient clinic referrals, 1285 (27%) were managed without a clinic appointment. More than half (54%) of the requests for paediatric assessment unit (PAU) admission were managed alternatively, typically with advice only or a rapid access clinic appointment. This has reversed the increasing trend of PAU admissions from primary care of preceding years. Financial analysis suggested the avoidance of these clinic appointments, and PAU admissions provided a substantial cost saving. Conclusions: Our results indicate that the PDM service has succeeded in reducing unnecessary hospital attendances by managing patients more effectively and strengthening partnerships with primary care. The service has received overwhelmingly positive feedback from GPs. This service could be replicated in other Trusts and developed in the future to facilitate further management of paediatric cases in a primary care setting.

Consent for babies born following surrogate pregnancies.

Surrogate pregnancies are becoming more common, but the law governing who can give consent following surrogate births is complex. Parental responsibility (PR) may be held by a variety of individuals, depending on the specific circumstances.We conducted a survey of paediatric medical staff within Health Education South West to establish knowledge regarding consent for a baby before a parental or adoption order is obtained. Our results showed that 19% of the 47 respondents answered all scenarios correctly. 43% of respondents knew that the surrogate mother had PR in all scenarios; however, 13% incorrectly assumed that either intended parent always had PR. Knowledge of other individuals who could provide consent in the scenarios was variable.Our survey revealed poor understanding regarding medicolegal aspects of consent in these complex situations, emphasising the need for more specific published guidance for primary and secondary healthcare professionals encountering these babies in the early postnatal period.

Ca2+ removal by the plasma membrane Ca2+-ATPase influences the contribution of mitochondria to activity-dependent Ca2+ dynamics in Aplysia neuroendocrine cells.

After Ca(2+) influx, mitochondria can sequester Ca(2+) and subsequently release it back into the cytosol. This form of Ca(2+)-induced Ca(2+) release (CICR) prolongs Ca(2+) signaling and can potentially mediate activity-dependent plasticity. As Ca(2+) is required for its subsequent release, Ca(2+) removal systems, like the plasma membrane Ca(2+)-ATPase (PMCA), could impact CICR. Here we examine such a role for the PMCA in the bag cell neurons of Aplysia californica CICR is triggered in these neurons during an afterdischarge and is implicated in sustaining membrane excitability and peptide secretion. Somatic Ca(2+) was measured from fura-PE3-loaded cultured bag cell neurons recorded under whole cell voltage clamp. Voltage-gated Ca(2+) influx was elicited with a 5-Hz, 1-min train, which mimics the fast phase of the afterdischarge. PMCA inhibition with carboxyeosin or extracellular alkalization augmented the effectiveness of Ca(2+) influx in eliciting mitochondrial CICR. A Ca(2+) compartment model recapitulated these findings and indicated that disrupting PMCA-dependent Ca(2+) removal increases CICR by enhancing mitochondrial Ca(2+) loading. Indeed, carboxyeosin augmented train-evoked mitochondrial Ca(2+) uptake. Consistent with their role on Ca(2+) dynamics, cell labeling revealed that the PMCA and mitochondria overlap with Ca(2+) entry sites. Finally, PMCA-dependent Ca(2+) extrusion did not impact endoplasmic reticulum-dependent Ca(2+) removal or release, despite the organelle residing near Ca(2+) entry sites. Our results demonstrate that Ca(2+) removal by the PMCA influences the propensity for stimulus-evoked CICR by adjusting the amount of Ca(2+) available for mitochondrial Ca(2+) uptake. This study highlights a mechanism by which the PMCA could impact activity-dependent plasticity in the bag cell neurons.

Ring substitution influences oxidative cyclisation and reactive metabolite formation of nordihydroguaiaretic acid analogues.

Nordihydroguaiaretic acid (NDGA) is a natural polyphenol with a broad spectrum of pharmacological properties. However, its usefulness is hindered by the lack of understanding of its pharmacological and toxicological pathways. Previously we showed that oxidative cyclisation of NDGA at physiological pH forms a dibenzocyclooctadiene that may have therapeutic benefits whilst oxidation to an ortho-quinone likely mediates toxicological properties. NDGA analogues with higher propensity to cyclise under physiologically relevant conditions might have pharmacological implications, which motivated this study. We synthesized a series of NDGA analogues which were designed to investigate the structural features which influence the intramolecular cyclisation process and help to understand the mechanism of NDGA's autoxidative conversion to a dibenzocyclooctadiene lignan. We determined the ability of the NDGA analogues investigated to form dibenzocyclooctadienes and evaluated the oxidative stability at pH 7.4 of the analogues and the stability of any dibenzocyclooctadienes formed from the NDGA analogues. We found among our group of analogues the catechols were less stable than phenols, a single catechol-substituted ring is insufficient to form a dibenzocyclooctadiene lignan, and only compounds possessing a di-catechol could form dibenzocyclooctadienes. This suggests that quinone formation may not be necessary for cyclisation to occur and the intramolecular cyclisation likely involves a radical-mediated rather than an electrophilic substitution process. We also determined that the catechol dibenzocyclooctadienes autoxidised at comparable rates to the parent catechol. This suggests that assigning in vitro biological activity to the NDGA dibenzocyclooctadiene is premature and requires additional study.

Electrical coupling between Aplysia bag cell neurons: characterization and role in synchronous firing.

In neuroendocrine cells, hormone release often requires a collective burst of action potentials synchronized by gap junctions. This is the case for the electrically coupled bag cell neurons in the reproductive system of the marine snail, Aplysia californica. These neuroendocrine cells are found in two clusters, and fire a synchronous burst, called the afterdischarge, resulting in neuropeptide secretion and the triggering of ovulation. However, the physiology and pharmacology of the bag cell neuron electrical synapse are not completely understood. As such, we made dual whole cell recordings from pairs of electrically coupled cultured bag cell neurons. The junctional current was nonrectifying and not influenced by postsynaptic voltage. Furthermore, junctional conductance was voltage independent and, not surprisingly, strongly correlated with coupling coefficient magnitude. The electrical synapse also acted as a low-pass filter, although under certain conditions, electrotonic potentials evoked by presynaptic action potentials could drive postsynaptic spikes. If coupled neurons were stimulated to spike simultaneously, they presented a high degree of action potential synchrony compared with not-coupled neurons. The electrical synapse failed to pass various intracellular dyes, but was permeable to Cs(+), and could be inhibited by niflumic acid, meclofenamic acid, or 5-nitro-2-(3-phenylpropylamino)benzoic acid. Finally, extracellular and sharp-electrode recording from the intact bag cell neuron cluster showed that these pharmacological uncouplers disrupted both electrical coupling and afterdischarge generation in situ. Thus electrical synapses promote bag cell neuron firing synchrony and may allow for electrotonic spread of the burst through the network, ultimately contributing to propagation of the species.

The UVA and aqueous stability of flavonoids is dependent on B-ring substitution.

Flavonols such as kaempferol and quercetin are believed to provide protection against ultraviolet (UV)-induced damage to plants. Recent in vitro studies have examined the ability of flavonols to protect against UV-induced damage to mammalian cells. Stability of flavonols in cell culture media, however, has been problematic, especially for quercetin, one of the most widely studied flavonols. As part of our investigations into the potential for flavonols to protect skin against UV-induced damage, we have determined the stability of a series of flavonols that differ only in the number of substituents on the B-ring. We measured the stability of these flavonols over time to UVA radiation, Dulbecco's modified Eagle's medium (DMEM), and Dulbecco's phosphate-buffered saline (DPBS) using high performance liquid chromatography with UV detection (HPLC-UV). The identification of the breakdown products of flavonols was accomplished by using a hybrid quadrupole linear ion trap mass spectrometer coupled with liquid chromatography. Tandem mass spectrometric analysis (MS/MS) of flavonol photoproducts was confirmed by comparing with the known standard samples. We have determined that flavonol stability decreases with increasing B-ring substitution, suggesting that future investigation of potential photoprotective flavonols will need to be cognizant of this trend.

A case of septicaemic anthrax in an intravenous drug user.

BACKGROUND: In 2000, Ringertz et al described the first case of systemic anthrax caused by injecting heroin contaminated with anthrax. In 2008, there were 574 drug related deaths in Scotland, of which 336 were associated with heroin and or morphine. We report a rare case of septicaemic anthrax caused by injecting heroin contaminated with anthrax in Scotland. CASE PRESENTATION: A 32 year old intravenous drug user (IVDU), presented with a 12 hour history of increasing purulent discharge from a chronic sinus in his left groin. He had a tachycardia, pyrexia, leukocytosis and an elevated C-reactive protein (CRP). He was treated with Vancomycin, Clindamycin, Ciprofloxacin, Gentamicin and Metronidazole. Blood cultures grew Bacillus anthracis within 24 hours of presentation. He had a computed tomography (CT) scan and magnetic resonance imagining (MRI) of his abdomen, pelvis and thighs performed. These showed inflammatory change relating to the iliopsoas and an area of necrosis in the adductor magnus.He underwent an exploration of his left thigh. This revealed chronically indurated subcutaneous tissues with no evidence of a collection or necrotic muscle. Treatment with Vancomycin, Ciprofloxacin and Clindamycin continued for 14 days. Negative Pressure Wound Therapy (NPWT) device was applied utilising the Venturi™ wound sealing kit. Following 4 weeks of treatment, the wound dimensions had reduced by 77%. CONCLUSIONS: Although systemic anthrax infection is rare, it should be considered when faced with severe cutaneous infection in IVDU patients. This case shows that patients with significant bacteraemia may present with no signs of haemodynamic compromise. Prompt recognition and treatment with high dose IV antimicrobial therapy increases the likelihood of survival. The use of simple wound therapy adjuncts such as NPWT can give excellent wound healing results.

Porfimer sodium photodynamic therapy in the treatment of early oesophageal carcinoma.

BACKGROUND: The gold standard treatment of early oesophageal carcinoma is oesophagectomy but the elderly population affected are often medically unfit for this radical intervention and less invasive curative options are required. We describe our experience of porfimer sodium photodynamic therapy (PDT) as an alternative to surgery in such a patient group. METHODS: From 1999 to 2005 28 oesophageal cancer patients were found to have early stage disease based initially on endoscopy/CT and latterly on CT/endoscopic ultrasound (EUS) criteria. Although potentially suitable for major surgical resection these patients were judged to be medically unfit and were selected to have PDT. Patients were followed up endoscopically at 6-12-week intervals indefinitely with biopsy of the treated area. RESULTS: 18/28 patients had an initial complete response 8 weeks post procedure. One patient died before reassessment of unrelated disease. Nine patients were non-responders. 7/18 complete responders remained disease free for a mean follow up period of 1166 days (249-2019). 11/18 developed recurrent local disease treated with further PDT with a median survival of 770 days (254-2049). Fourteen patients had EUS staging which accurately predicted response: all T1N0 patients (9/14) had initial complete response to treatment although 5/9 have required further PDT. All remain disease free at a follow up of 1103 days (249-2019). No patients with T2/3N0 disease had complete response to treatment. The major complication of PDT encountered was stricture formation which occurred in 50% of cases and required a median of five dilations (range 1-31). CONCLUSIONS: Porfimer sodium PDT is a potentially curative treatment in patients with early oesophageal carcinoma who may be unfit or unwilling to undergo major surgery.